Glycoprotein D (gD) of herpes simplex virus (HSV) is required for successful infection. It is strongly implicated in virus penetration, in viral-induced cell-cell fusion, in exclusion of progeny virus and possibly, in stable attachment. However, the specific events that are mediated by gD and how it performs these functions is not yet known. The objective of this proposal is to determine the molecular basis of gD function for herpesviruses using biochemical, genetic, immunochemical and electron microscopy approaches. The specific aims are (a) to determine the step in HSV penetration that gD mediates that is hypothesized to differ form that mediated by other essential glycoproteins (gB and gH) (b) to determine other products besides gD that are required to mediate viral induced cell- cell fusion and (c) to determine functional similarity between gD and its homolog, gp50, in pseudorabies virus that it mediates a tighter adhesion between biological membranes. Evidence for or against this hypothesis will be provided by results from the proposed research. Understanding the molecular basis of gD function for HSV and PRV will provide information about critical events in herpesvirus entry and virus induced cell-cell fusion that will be relevant to other enveloped viruses which cause diseases. Since membrane fusion and membrane transit and frequent and essential biological events, this research will contribute to better understanding of this universal process.